The overarching aim of the Neurobiology Core is to provide intellectual leadership and practical assistance to studies on the mechanisms of HIV- induced neurodegeneration. Our laboratory has developed a unique set of technical and neurobiological resources that allow the comprehensive and dynamic study of the neurodegenerative processes associated with HIV infection. The Core Resources Objectives will be to 1) provide analytic techniques that will facilitate studies on HIV-mediated neuropathogenesis; 2) provide technical assistance and consultation on state-of-the-art molecular and cellular approaches; 3) support preliminary studies on neuropathogenesis that envision analyses at the molecular and cellular levels; 4) provide mentorship for students and junior faculty in the theory and techniques of neurobiology and neuropathology; 5) collaborate with the Coordinating Core to disseminate information on HIV-related neuropathogenesis. In cooperation with HNRC-affiliated colleagues in San Diego, Pittsburgh, Boston, , and London, the Core Scientific Aims will be to 1) provide quantitative analysis of neurodegeneration in the brain, 2) provide quantitative analysis of viral burden in the brain, and 3) provide quantitative analysis of mRNA levels of chemokines, cytokines and other mediators of HIV cell injury to the pathway in HIV-mediated neurodegeneration. For this purpose, GFAP- gp120 transgenic mice will be crossed with the PDGFbeta-GSK3beta transgenic mice. This will determine if over-expression of GSK3beta enhances gp120 neurotoxicity, and whether down-regulation of GSK3beta is a neuroprotective. This proposal will serve to consolidate these services into a single well-focused resources that would aim at reaching more investigators interested in neuroAIDS research.